Increased thymic output during acute measles virus infection

Abstract

Measles virus infects thymic epithelia, induces a transient lymphopenia, and impairs cell-mediated immunity, but thymic function during measles has not been well characterized. Thirty Zambian children hospitalized with measles were studied at entry, hospital discharge, and at 1-month follow-up and compared to 17 healthy children. During hospitalization, percentages of naïve (CD62L+, CD45RA+) CD4+ and CD8+ T lymphocytes decreased (P = 0.01 for both), and activated (HLA-DR+, CD25+, or CD69+) CD4+ and CD8+ T lymphocytes increased (P = 0.02 and 0.03, respectively). T-cell receptor rearrangement excision circles (TRECs) in measles patients were increased in CD8+ T cells at entry compared to levels at hospital discharge (P = 0.02) and follow-up (P = 0.04). In CD4+ T cells, the increase in TRECS occurred later but was more sustained. At discharge, TRECs in CD4+ T cells (P = 0.05) and circulating levels of interleukin-7 (P = 0.007) were increased compared to control values and remained elevated for 1 month, similar to observations in two measles virus-infected rhesus monkeys. These findings suggest that a decrease in thymic output is not the cause of the lymphopenia and depressed cellular immunity associated with measles.

FIG. 1.

Box plots of the percent naïve, memory, and activated CD4⁺ and CD8⁺ lymphocytes in children with measles and control children. Percent CD4⁺ (A) and CD8⁺ (B) T lymphocytes with naïve phenotype (CD45RA⁺, CD62L⁺), percent CD4⁺ (C) and CD8⁺ (D) T lymphocytes with memory phenotype (CD45RO⁺, CD25⁻, CD69⁻, HLA-DR2⁺), and percent CD4⁺ (E) and CD8⁺ (F) T lymphocytes with activated phenotype (CD25⁺, CD69⁺, or HLA-DR⁺) in children with measles at study entry (n = 30), hospital discharge (n = 19 to 20), and 1-month follow-up (n = 10) and in control children (n = 17). P values were calculated by using the Mann-Whitney U test.

FIG. 2.

Box plots of the log number of TRECs per 10⁶ CD4⁺ (A) and CD8⁺ (B) T lymphocytes in children with measles and control children. Entry, study entry; Disch, hospital discharge; 1 mo, 1-month follow-up. P values were calculated by using the Mann-Whitney U test.

FIG. 3.

Box plots of plasma IL-7 levels in children with measles and control children. Group sizes were as follows: study entry (n = 49), hospital discharge (n = 45), 1-month follow-up (n = 31), and controls (n = 18). P values were calculated by using the Mann-Whitney U test.

FIG. 4.

Mean percent CD4⁺ (A) and CD8⁺ (B) T lymphocytes with naïve phenotype (CD45RA⁺) and TRECs per 10³ CD4⁺ (C) and CD8⁺ (D) lymphocytes during acute and convalescent phases of measles in two rhesus monkeys.