LOS INSTRUMENTOS QUE NECESITA
CÓMO DISTINGUIR PROBLEMAS PARECIDOS
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100. KUNA K, ^ULO F, RADO[ M, HAUER D 1994 Production of tumor necrosis factor-α by spleen cells. Period biol 96:13–20
101. ^ULO F., ERCEG D, VIIK P 1998 The effect of vasoactive intestinal peptide on production of tumor necrosis factor-α in vivo. Int J Immunother 14: 83–7
102. VUKADIN S, RADO[ M, MUBRIN Z, BRINAR V, ^ULO F 1997 The level of tumor necrosis-alpha factor in cerebrospinal fluid of patients with multiple sclerosis. Neurol Croat 46: 73–84
103. RADO[ J, RADO[ M, HORVAT B, ^ULO F 2004 Interleukin-1b but not several other cytokines abrogates tolerance to contact allergen. Periodicum
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104. AURER A, ALEKSI] J, IVI]-KARDUM M, AURER J, ^ULO F 2001 Nitric oxide synthesis decreased in periodonitis. J Clin Periodontol 28: 565–8
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106. MOROVIC-VERGLES J, CULO M-I, GAMULIN S, ^ULO F 2008 Cyclic adenosine 5’-monophosphate (cAMP) in synovial fluid of rheumatoid ar- thritis and osteoarthritis patients. Rheumatol Int. (in press)
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110. MARU[I] M 1979 Immunological recovery of thymectomized and sham thymectomized lethally irradiated mice reconstituted with syngeneic bone mar- row cells. Experientia 35: 683–4
111. RADI] I, VU^AK I, MILO[EVI] J, MARU[I] A, VUKI^EVI] S, MARU[I] M 1988 Immunosuppression induced by talc granulomatosis in the rat. Clin Exp Immunol 73: 316–21
112. ME[TROVI] J, KO[UTA D, GO[OVI] S, DENOBLE P, RADOJKOVI] M, AN\ELINOVI] [, BA[I] I, MARU[I] M 1990 Suppression of rat
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113. MARU[I] A, DJIKI] I, MARU[I] M 1990 Cellular and morphological changes in lymphoid organs after a single injection of interleukin 1-alpha in the mouse. Agents Actions 31: 280–4
114. VUKI^EVI] S, SOMOGYI L, MARTINOVI] I, @IC R, KLEINMAN HK, MARU[I] M 1992 Reconstituted basement membrane (Matrigel) influ- ences the survival and growth of murine tumors. Int J Cancer 50: 791–5
115. TRUTIN-OSTOVI] K, GOLUBI] M, MATOVI] M, MARU[I] M 1986 Incidence and growth of methylcholanthrene-induced tumors in mice with altered immunological status. Cancer Immunol Immunother 23: 130–6
116. SOMOGYI L, JUKI] T, BUKOVEC @, ^ULO F, MARU[I] M 1994 Gonadectomy abrogates sex differences in the effectiveness of chemical carcino- genesis in mice. Neoplasma 41: 17–9
117. BOGDANOVI] Z, ^ULO F, MARU[I] M 1993 Effect of three biological response modifiers on chemical carcinogenesis in mice. Neoplasma 40: 229–33
118. MARU[I] M 1978 Transfer of immunity by transfer of bone marrow cells: T-cell dependency. Cell Immunol 38: 440–9
119. MARU[I] M 1978 Transfer of immunity by transfer of bone marrow cells: a requirement for T-lymphocytes and sensitivity to cyclophosphamide. Exp
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120. SENJANOVI] M, MARU[I] M 1984 Bone marrow-derived T lymphocytes responsible for allograft rejection. Cell Immunol 87: 225–30
121. MARU[I] M 1988 A novel type of allogeneic skin graft rejection revealed through a delay in graft exposure to T lymphocytes. Transplant Proc 20: 294–5
122. MARU[I] M, ALLEGRETTI N, ^ULO F 1978 Influence of the thymus on the incidence of secondary and parabiotic disease. Experientia 34: 258–59
123. MARU[I] M, ALLEGRETTI N, ^ULO F 1976 Cell cooperation in abolition of tolerance to xenogeneic tumor. Cell Immunol 27: 26–35
124. MARU[I] M, GOODMAN JW, SHINPOCK SG 1977 Cooperation of nonsyngeneic tolerant lymphocytes: genetic restriction. Cell Immunol 33: 72–80
125. MARU[I] M, PERKINS EH 1979 In vivo cooperation of murine lymphocytes sharing one haplotype of transplantation genes: a requirement for tol- erance of the non-shared haplotype. J Immunol 122: 1116–20
126. MARU[I] M, PERKINS EH 1980 Cooperation of murine F1 T and parental B lymphocytes in rejection of a xenogeneic tumor: adaptive differentia- tion of B lymphocytes? Scand J Immunol 11: 609–21
127. MARU[I] M, PERKINS E H 1981 Genetic constraints of the immune response to Ehrlich ascites tumor in mice. Cell Immunol 62: 93–100
128. MARU[I] M 1979 Genetic restrictions of lymphocyte interactions. Period biol 81: 3–14
129. MARU[I] M, KINDRED B 1982 Failure of parental T cells to restore T-cell deficient F1 mice. Immunol Commun 11: 83-96
130. KLEIN J, MARU[I] M, NAGY Z A 1982 The seven rules of Mhc restriction. Transplant Proc 14: 581-3
131. NAGY Z A, IKEZAWA Z, MARU[I] M, BAXEVANIS C N, ISHII N, KLEIN J 1983,Ia antigens as restriction molecules in Ir-gene controlled T-cell proliferation. In: Ir genes, Past, Present and Future. (eds) Schwartz D, Shreffler DC. The Humana Press, Clifton NJ, SAD, p 425
132. MARU[I] M, NAGY Z A, KOSZINOWSKI U, KLEIN J 1982 Involvement of Mhc loci in immune responses that are not Ir gene controlled. Immu-
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133. VRANE[ Z, VARGA D, VU^AK I, JELI] I, MARU[I] M 1989 Lymphocyte content in the aging human thymus. Thymus 14: 265–6
134. MARU[I] M, TURKALJ-KLJAJI] M, PETROVE^KI M, U@AREVI] B, RUDOLF M, BATINI] D, UGLJEN R, ANI] D, ]AVAR @, JELI] I,
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135. MRSI] M, LABAR B, BOGDANI] V, NEMET D, PAVLETI] @, PLAV[I] F, DOBRI] I, MARU[I] M, FRANCETI] I, KA[TELAN A, KA-
LENI] S, VRTAR M, MARKULIN-GRGI] LJ, AURER I 1990 Combination of cyclosporine and methotrexate for prophylaxis of acute graft versus host disease after allogeneic bone marrow transplantation for leukemias. Bone Marrow Transplant 6: 137–41
136. LABAR B, BOGDANI] V, NEMET D, MRSI] M, VRTAR M, GRGI]-MARKULIN LJ, KALENI] S, VUJASINOVI] S, PRESE^KI V, JAKI]-RA-
ZUMOVI] J, MARU[I] M 1992 Total body irradiation with or without lung shielding for allogeneic bone marrow transplantation. Bone Marrow
Transplant 9: 343–7
137. LABAR B, MRSI] M, NEMET D, BOGDANI] V, RADMAN I, BOBAN D, BATINI] D, KALENI] S, VRTAR M, GRGI]-MARKULIN LJ,
KA[TELAN A, MARU[I] M 1994 Allogeneic bone marrow transplantation versus chemotherapy for patients with acute myelogenous leukaemia in first remission. Transplantationsmedizin 6: 235–9
138. BATINI] D, PAVLETI] @, KOLEVSKA T, BOGDANI] V, @ALUD I, NEMET D, MARU[I] M, LABAR B 1989 Lymphocyte subsets in normal human bone marrow harvested for routine clinical transplantation. Bone Marrow Transplant 4: 285–90
139. BATINI] D, MARU[I] M, PAVLETI] @, BOGDANI] V, U@AREVI] B, NEMET D, LABAR B. 1990 Relationship between differing volumes of bone marrow aspirates and their cellular composition. Bone Marrow Transplant 6: 103–7
140. MARU[I] A, DJIKI] I, VUKI^EVI] S, MARU[I] M. 1992 Demineralized bone matrix-induced endochondral bone formation in immunosup- pressed rats. Experientia 48: 783–5
141. SOMOGYI L, MARTINOVI] S, MARTINOVI] I, VUKI^EVI] S, MARU[I] M 1995 Synergistic effect of laminin and phorbol myristate acetate on the bone marrow stem cells. Croat Med J 36: 228–33
142. GR^EVI] D, BATINI] D, ASCENSAO JL, MARU[I] M 1999 Pre-treatment of transplant bone marrow cells with hydrocortisone and cyclosporin A alleviates graft-versus-host reaction in a murine allogeneic host-donor combination. Bone Marrow Transplant 23: 1145–52
64 Period biol, Vol 110, Suppl 1, 2008. 143. SU^I] M, KOLEVSKA T, KOPJAR B, KOSANOVI] M, DROBNJAK M, @ALUD I, MARU[I] M 1989 Accuracy of routine bitmap selection for
three white blood cell populations. Cytometry 10: 442–7
144. U@AREVI] B, BATINI] D, PETROVE^KI M, MARU[I] M 1991 Leukocyte membrane markers on cell populations defined by six flow cytomet- ric bitmaps. J Clin Lab Analysis 6: 17–23
145. SU^I] M, BOBAN D, MARKOVI]-GLAMO^AK M, PETROVE^KI M, MARU[I] M, LABAR B 1992 Prognostic significance of cytochemical
analysis of leukemic blasts (M1, M2). Med Oncol Tumor Pharmacother 9: 41–5
146. JAKI] RAZUMOVI] J, U@AREVI] B, PETROVE^KI M, MARU[I] M, RADMAN I, LABAR B 1992 AgNORs predictive value of prognosis in NHL: Comparison with flow cytometric cell cycle analysis. Leukem Lymphoma 7: 165–70
147. PETROVE^KI M, MARU[I] M, DE@ELI] G 1993 An algorithm for leukaemia immunophenotype pattern recognition. Med Inform 18: 11–21
148. BOBAN D, SU^I] M, MARKOVI]-GLAMO^AK M, U@AREVI] B, BATINI] D, MARU[I] M, NEMET D, LABAR B, HITREC V 1993 Cor-
relation of morphological FAB classification and immunophenotyping: Value in recognition of morphological, cytochemical and immunological char- acteristics of mixed leukaemias. Eur J Cancer 29(A): 1167–72
149. VU^KOVI] J, FORENPOHER G, MARU[I] M, U@AREVI] B, SABIONCELLO A, [TULA N, DUBRAV^I] M 1995 Significance of aneu-
ploidy in non-Hodgkin lymphomas. J Clin Lab Analysis 9: 343–6
150. PETROVE^KI M, NEMET D, KOLEVSKA T, MARU[I] M 1995 Granulocyte-monocyte colony forming unit content in autologous bone marrow transplants in patients with haematological malignancy. Eur J Clin Chem Clin Biochem 33: 687–91
151. VI[NJI] D, BATINI] D, MARU[I] M, BANFI] H 1995 Short-term and long-term effects of phorbol 12-myristate 13-acetate and different inhibi- tors on the ability of bone marrow cells to form colonies in vitro. Eur J Clin Chem Clin Biochem 33: 679–86
152. PETROVE^KI M, U@AREVI] B, MARU[I] M, DE@ELI] G J 1996 Analysis of data on leukocyte surface markers for recognition of leukemia/lym- phoma phenotype pattern. Clin Biochem 29: 21–5
153. VI[NJI] D, BATINI] D, LASI] Z, KNOTEK M, MARU[I] M, BANFI] H 1995 Phorbol 12-myristate 13-acetate mediated signalling in murine bone marrow cells. Biochem J 310: 163–70
154. VU^KOVI] J, FORENPOHER G, MARU[I] M, U@AREVI] B, ZEMUNIK 1998 T Prognostic relevance of non-Hodgkin’s lymphomas cell cycle data. Neoplasma 45: 332–5
155. VRANE[ Z, POLJAKOVI] Z, MARU[I] M 1989 Natural killer cell number and activity in multiple sclerosis. J Neurol Sci 94: 115–23
156. VRANE[ Z, U@AREVI] B, BATINI] D, PERI] M, POLJAKOVI] Z, MARU[I] M 1990 Natural killer (NKH-1+) cell number and activity in health and disease. Med Lab Sci 47: 108–12
157. HARJA^EK M, BATINI] D, SARNAVKA V, U@AREVI] B, MARDE[I] D, MARU[I] M 1990 Case report: Immunological aspects of progeria (Hutchinson-Gilford syndrome) in a 15-month old child. Europ J Pediat 150: 40–2
158. PERI] M, VRANE[ Z, MARU[I] M 1991 Immunological disturbances in anaesthesiology personnel chronically exposed to high occupational concen- trations of halothane and nitrous oxide. Anaesthesia 466: 531–7
159. PERI] M, PETROVE^KI M, MARU[I] M 1994 Age-dependent immunohaematologic disturbances in anaestesiology personnel chronically exposed to high occupational concentrations of halothane and nitrous oxide. Anaesthesia 49: 1022–7
160. VE^EK N, NOLA M, MARU[I] M, BABI] D, U@AREVI] B, SABIONCELLO A, PETROVE^KI M, LJUBI]-RA^UNICA N, MARINOVI] T
1994 Tumor cell-cycle in patients with stage I endometrial carcinoma. Gynecol Oncol 53: 38–43
161. VE^EK N, NOLA M, MARU[I] M, ILI] D, BABI] D, PETROVE^KI M, NIKOLI] S, MARINOVI] T, JUKI] D, VE^EK N, Jr. 1994 Prognos- tic value of steroid hormone receptors concentration in patients with endometrial carcinoma. Acta Obstetr Gynecol Scand 73: 730–3
162. BU[I] T, PUNDA-POLI] V, BANOVI] I, MARU[I] M 1994 Effect of antimicrobial treatment on cytologic findings in women with abnormal Pa- panicolaou smeras. The CERVIX and the lower female genital tract 12: 120–2
163. U@AREVI] B, PETROVE^KI M, MARU[I] M, JAKI]-RAZUMOVI] J, HUTINEC Z, SABIONCELLO A, GAMULIN S 1998 Prognostic sig-
nificance of cell cycle parameters in lymphoproliferative ductal breast carcinoma. J Clin Lab Analysis 12: 131–6
164. NOLA M, JUKI] S, ILI]-FORKO J, BABI] D, U@AREVI] B, PETROVE^KI M, SUCHANEK E, [KRABLIN S, DOTLI] S, MARU[I] M 1999 Effects of Tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow-cytometry in endometrial carci- noma. Gynecol Oncol 72: 331–6
165. KATU[IN D, U@AREVI] B, PETROVE^KI M, MLINAC-LUCIJANI] M, MARU[I] M, MAREKOVI] Z 2000 Clinical, histopathological and
flow-cytometric properties of incidental renal cell carcinomas. Urol Res 28: 52–6
166. \ANI] D, MARU[I] M, U@AREVI] B, MILI^I] D 2000 Prognostic factors in squamous cell carcinoma of the larynx. ORL 62: 143–8
167. MARKELJEVI] J, MARU[I] M, U@AREVI] B, PETROVE^KI M, TRUTIN-OSTOVI] K, ^IKE[ N, BATINI] D, BABI]-NAGLI] \, HOR-
VAT Z 1991 T cell subset composition in remission phase of systemic connective tissue diseases. J Clin Lab Immuno 35: 33–9
168. MARKELJEVI] J, MARU[I] M, U@AREVI] B, PETROVE^KI M, ^IKE[ N, BABI]-NAGLI] \, HORVAT Z 1991 Natural killer cell number and activity in remission phase of systemic connective tissue diseases. J Clin Lab Immunol 35: 133–8
169. SOMOGYI L, ^IKE[ N, MARU[I] M 1993 Evaluation of criteria contributions for the classification of systemic lupus erythematosus. Scand J Rheu-
matol 22: 58–62
170. MARKELJEVI] J, U@AREVI] B, BATINI] D, BO@IKOV J, ^IKE[ N, BABI]-NAGLI] \, HORVAT Z, MARU[I] M 1994 Peripheral blood
CD5+ B cell subset in remission phase of systemic connective tissue diseases. J Rheumatol 21: 2225–30
171. BATINI] D, BO@I^EVI] M, KRSTULOVI] A, BOSNI] D, SENTI] M, MARKELJEVI] J, MALENICA B, ^IKE[ N, MARU[I] M 1996 Bind-
ing of anti-double stranded (ds) DNA-positive sera to denatured (d) DNA and synthetic poly(dA-dT)xpoly(dA-dT) double stranded copolymer in and ELISA format. Eur J Clin Chem Clin Biochem 34: 343–7
172. KARAMAN-KRALJEVI] K, [TAMBUK V, [TAMBUK N, MARU[I] M, KA[TELAN A, U@AREVI] B, BATINI] D 1996 Etiology and clinical
173. CVITANOVI] S, MARU[I] M, ZEKAN LJ, KOHLER-KUBELKA N 1986 Allergy induced by Parietaria officinalis pollen in Southern Croatia. Al-
lergy 41: 543–5
174. CVITANOVI] S, GRBI] D, ZEKAN LJ, BOBAN M, VRDOLJAK E, PARPURA V, PETROVI] S, MARU[I] M 1989 Hypersensitivity to P. Offici- nalis pollen: Correlation of IgE with skin testing methods. Allergol Immunopathol 17: 197–200
175. CVITANOVI] S, ZEKAN LJ, MARU[I] M 1989 Occurence and specificity of IgE antibodies to isocyanates in occupationally exposed work ers. Int Arch
Occup Environ Health 61: 483–6
176. CVITANOVI] S, MARU[I] M, JURI^I] M, VRDOLJAK E, PETROVE^KI M, ROZGA A, STAVLJENI]-RUKAVINA A 1993 Hypersensitivity
to Parietaria officinalis pollen in the newcomers to the area with the plant. Allergy 48: 592–7
177. CVITANOVI] S, MARU[I] M 1994 Hypersensitivity to pollen allergens at the East Adriatic coast. J Invest Allergol Clin Immunol 4: 96–100
178. CVITANOVI] S, ZEKAN LJ, ^APKUN V, MARU[I] M 1994 Specific hyposensitization in patients allergic to Parietaria officinalis pollen allergen. J
Invest Allergol Clin Immuno 4: 283–90
179. MANDI] Z, MARU[I] M, BORANI] M 2004 Low levels of immunoglobulin A in children with intrinsic asthma: a possible protection against at- opy. Med Hypotheses 62(4):600–4
180. ALLEGRETTI N, TARADI M, MALENICA B 1977 Tolerance and prevention of tumor growth in immune deficient mice In Detection and Preven- tion and Detection of Cancer. Neighburg H (ed), New York and Basel, p 479
181. TARADI M 1980 Microenvironmental factors in tumor growth. Period biol 82: 103–107
182. @UPAN^I] V, KUKOLJA TARADI S, ANDREIS I, TARADI M 1993 The effect of macrophage depletion on the induction of EAE. Period biol 95(3): 335–40
183. CRNOGORAC-JUR^EVI] T, JUR^EVI] S, TARADI M, SABOLI] T 1989 Proton transport mechanisms in rat peritoneal macrophages; proper- ties of Na+- H+ exchanger. Period biol 91: 327–35
184. KUKOLJA TARADI S, LUKINOVI]-[KUDAR V, TARADI M 2004 Prevention of experimental autoimune ancephalomyelitis by administration of myelin basic protein in rats. Period biol 106: 389–96
185. URANO M, TARADI M, KUKOLJA TARADI S 1991 Enhancement of the thermal response of murine tumour and normal tissues by a streptococcal preparation, OK-432 (Picibanil). Int J of Hyperthermia 7: 113–23
186. TARADI M, URANO M, KUKOLJA TARADI S, MARUYAMA Y 1991 Augmentation of mouse natural killer cell activity by combined hyperthermia and streptococcal preparation, OK-432 (Picibanil) treatment. Int J of Hyperthermia 7: 653–65
187. KUKOLJATARADI S, TARADI M, URANO M 1992 Effect of thermoimmunotherapy with OK-432 on the development of spontaneous lung metas- tases in mice. Int J of Hyperthermia 8: 221–26
188. KUKOLJA TARADI S, TARADI M 2004 Expanding Traditional Physiology Class with Asynchronous Online Discussions and Collaborative Projects.
Adv Physiol Educ 28: 73–8
189. KUKOLJA TARADI S, TARADI M, RADI] K, POKRAJAC N 2005 Blending Problem-Based Learning with Web Technology Positively Impacts Stu- dent Learning Outcomes in Acid-Base Physiology. Adv Physiol Educ 29: 35–9
190. KUKOLJA TARADI S, TARADI M, RADI] K 2005 Integration of online formative assessments into medical education: experience from University of Zagreb Medical School, Croatia. Natl Med J India 18(1): 261–2
Period biol, Vol 110, Suppl 1, 2008. 67
ANA MARU[I]
Department of Anatomy, University of Zagreb, School of Medicine [alata 11, 10000 Zagreb, Croatia
E-mail: [email protected]
OSTEOIMMUNOLOGY AS A NOVEL RESEARCH FIELD
T
he interdisciplinary field of osteoimmunology, focusing on the close relationship between the immune and skeletal sys- tems, has recently attracted much attention due to the observations that bone metabolism is often disturbed by an abnor- mal response of the immune system and that mice lacking immunomodulatory molecules often exhibit an unexpected bone phenotype (1–3). Within the bone marrow, the bone and the immune system are anatomically, developmentally and func- tionally related. Bone and immune cells share the same progenitors, their differentiation may be driven by the same support- ing cells, and the same regulatory molecules play a crucial role in the regulation of both bone and immune cell differentiation and activity (3). Therefore, the role of any regulatory molecule within the bone marrow microenvironment should always be considered in studying both the immune and bone cells.In addition to the investigation in the field of transplantation immunology and hematology (4–9), our research group opened the new and intriguing field of osteoimmunology some 13 years ago, searching for both bone and immune effects of the same regulatory factor. Interestingly, one of our first studies showed that the complexity of the genetic regulation of cell functions was visible not only as a variation in the immune response among different inbred mouse strains or differences in the peak bone mass, but also in the ability to form new bone after an osteoinductive stimulus (10).
Our group developed two experimental models of osteoinduction in the mouse, which replicate endochondral or mem- branous bone formation during fetal development. We were the first to show that blood can serve as a carrier for osteoinduc- tive bone morphogenetic proteins (BMP) instead of collagen or calcified matrices, which led to the development of an in vivo model of bone induction by recombinant human (rh)BMP-2 administered in a blood clot (11). We also adapted to the mouse model the method of stimulating membranous bone induction by mechanical ablation of the tibial bone marrow (12, 13).
Studying interactions between cells of the immune system andthe bone
Both major lymphocyte populations are involved in the regulation of bone metabolism. Our group studied the role of B- lymphocytes in the regulation of new bone induction and regeneration, using mice produced by targeted disruption of the m- chain (mMT mutation), in which the development of B-lymphocytes is arrested at the pre-B-cell maturation stage (12). Us- ing the model of new bone induction by implantation of rhBMP-2 in a syngeneic blood clot (11), we showed that the lack of mature B-lymphocytes in these mice did not directly affect bone formation, but rather enhanced recruitment and prolifera- tion of osteoprogenitor cells (12). In addition, to be involved in the regulation of bone cells differentiation, B-lineage cell pop- ulation contains progenitors that can differentiate into osteoclasts in vitro. Based on these findings, we investigated whether estrogen withdrawal by ovariectomy affects the ability of receptor activator of NF-kB ligand (RANKL) and macrophage col- ony-stimulating factor (M-CSF) to stimulate formation of osteoclasts in unfractioned and B-cell lineage marker CD45R-pos- itive murine bone marrow cell culture, and showed that CD45R expression identified a subset of murine bone marrow cells whose ability to form osteoclasts in vivo is regulated by estrogen (14).
By investigating the role of T-lymphocytes in the regulation of bone metabolism, we first showed that T-lymphocyte de- pletion by neonatal thymectomy in rats primed the osteoinductive sequences of endochondral new bone formation (15). Then we showed that bone turnover in mice deficient for b2-microglobulin, which is a constituent of the class I major histocompat-
ibility complex molecule and is crucial for its normal function in cell recognition by CD8+ subpopulation of T-lymphocytes, was adequate for the stage of their skeletal maturation and similar to that in their wild-type littermates (16). Finally, we as- sessed the role of T-lymphocytes in endochondral new bone formation in the model of in vivo rhBMP-2 implantation in CD4+ and CD8+ T-lymphocyte depleted mice (3). By demonstrating increased cartilage formation in mice depleted of CD4+ and CD8+ T-lymphocyte subsets in vivo, we confirmed that T-lymphocytes play an important role in the endochondral sequence of new cartilage and bone formation.
Our group also provided a body of evidence that T-lymphocytes play an important role in the regulation of osteoclast dif- ferentiation and function. To investigate the role of T-lymphocytes in osteoclast differentiation, we selectively depleted CD4+ and CD8+ T- lymphocyte subsets in vivo and analyzed osteoclastogenic potential of the murine bone marrow and splenic progenitors after stimulation with 1,25-(OH)2 vitamin D3 or RANKL and M-CSF (17). T-lymphocyte depletion did not af- fect osteoclast formation from bone marrow and spleen cells treated with RANKL and M-CSF, but it significantly stimulated osteoclastogenesis in bone marrow cultures stimulated with 1,25-(OH)2 vitamin D3. This effect was mediated by enhanced