Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: no requirement for CD8+ T cells or B cells.
We wished to determine whether CD4+ T cells could reject a skin graft that was discordant for a single minor transplantation Ag in the absence of CD8+ T cells or Ab. Transgenic A1(M) mice were constructed that express the rearranged V beta 8.2 and V alpha 10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-Ek. In addition, the RAG-1(-/-) background was bred onto these mice to eliminate any endogenous TCR rearrangements. As expected, clonal deletion was found to be complete in the thymus of male A1(M) x RAG-1(-/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female A1(M) x RAG-1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that no CD8+ T cells or surface Ig+ B cells were present. An immunofluorescent analysis of spleen cells after grafting showed that the majority of T cells expressed activation markers (CD44, CD25, and intracytoplasmic IL-2) and a significant proportion were making IFN-gamma and IL-4. Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin.
Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom.
D
D
Zelenika
E
E
Adams
A
A
Mellor
E
E
Simpson
P
P
Chandler
B
B
Stockinger
H
H
Waldmann
S P
SP
Cobbold
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015704:CD4 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D016654:Genes, RAG-1 / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012727:Sex Characteristics; D016038:Skin Transplantation / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta