IL-4 producing CD4+ TCR alpha beta int liver lymphocytes: influence of thymus, beta 2-microglobulin and NK1.1 expression.

The present report describes developmental, phenotypic and functional features of unconventional CD4+ TCR alpha beta lymphocytes. In C57BL/6 mice, the majority of liver lymphocytes expressing intermediate intensity of TCR alpha beta (TCR alpha beta int) are CD4+ NK1.1+ and express a highly restricted TCR V beta repertoire, dominated by V beta 8 with some contribution by V beta 7 and V beta 2. Although these cells express the CD4 co-receptor, they are present in H2-1 A beta (A beta)-/- gene disruption mutants but are markedly reduced in beta 2-microglobulin (beta 2m)-/- mutant mice and hence are beta 2m dependent. Thymocytes expressing the CD4+ NK1.1+ TCR alpha beta phenotype are also beta 2m contingent, suggesting that these two T lymphocyte populations are related. The CD4+ NK1.1+ TCR alpha beta lymphocytes in liver and thymus share several markers such as LFA-1+, CD44+, CD5+, LECAM-1- and IL-2R alpha-. The CD4+ NK1.1+ TCR alpha beta int liver lymphocytes were not detected in athymic nu/nu mice. We conclude that beta 2m expression is crucial for development of the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes and that thymus plays a major role. CD4+ TCR alpha beta int liver lymphocytes were also identified in NK1.1- mouse strains, there lacking the NK1.1 marker. We assume that the NK1.1 molecule is a characteristic marker of the CD4+ TCR alpha beta int liver lymphocytes in NK1.1+ mouse strains, although its expression is not obligatory for their development. The liver lymphocytes from beta 2m+/-, but not from beta 2m-/-, mice are potent IL-4 producers in response to CD3 or TCR alpha beta engagement and the IL-4 production by liver lymphocytes was markedly reduced by treatment with anti-NK1.1 mAb. We conclude that the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes are capable of producing IL-4 in response to TCR stimulation.