Functional analysis of cloned germinal center CD4+ cells with natural killer cell-related features. Divergence from typical T helper cells

Granular lymphocytes co-expressing the Leu-7 (NK-related) and CD4 (T helper cell) markers are selectively localized in the germinal centers of lymphoid tissues. Leu-7⁺ cells (>98% of which co-expressed CD4) were isolated from inflammatory tonsils and were cloned by the limiting dilution technique. Clones were analyzed for their phenotypic and functional characteristics. CD4⁺-Leu-7⁺ cell-derived clones retained their CD3 and CD4 surface antigens, lost the Leu-7 marker, and acquired HLA-DR determinants. In comparison with clones derived from peripheral blood or tonsil CD4⁺ cells, CD4⁺-Leu-7⁺ tonsil cell-derived clones showed similar low frequencies of cytotoxic precursors. In contrast, the frequency of interleukin 2 (IL 2) and B cell growth factor producing clones was much lower for tonsil CD4⁺-Leu-7⁺ cells than for CD4⁺ blood or tonsil progenitors. We conclude that germinal center CD4⁺-Leu-7⁺ cells are a subset of T cells unable to produce IL 2 in response to phytohemagglutinin or anti-CD3 stimulation, which is effective on the majority of T helper cells.